2 LAY SUMMARY Sterilised Water for Injections This is a summary of the Public Assessment Report (PAR) for Sterilised Water for Injections (PL 08801/0057). It explains how Sterilised Water for Injections was assessed and its authorisation recommended, as well as its conditions of use. It is not intended to provide practical advice on how to use Water for Injections. For practical information about using Sterilised Water for Injections, patients should read the package leaflet or contact their doctor or pharmacist. What is Sterilised Water for Injections and what is it used for? Sterilised Water for Injections is a special type of water that has been carefully cleaned and purified so it does not contain any other ingredients. Sterilised Water for Injections is called a diluent because its main use is for diluting and preparing medicines before use. Sterilised Water for Injections is used to dissolve and dilute other drugs that require mixing with water before they can be given as an injection or an infusion (a drip) into your veins, muscles or other tissues in the body. How does Sterilised Water for Injections work? Sterilised Water for Injections dissolves and dilutes other drugs that require mixing before they can be given as an injection or an infusion (a drip). It contains no active ingredients. How is Sterilised Water for Injections used? Sterilised Water for Injections is used to dissolve and dilute other medicines before it given by a health professional as an injection or infusion (a drip). In the preparation of the medicine for use, the required volume of Sterilised Water for Injections will vary, depending on the medicine to which it is added. The health professional will use the correct amount of Sterilised Water for Injections to dissolve or dilute the medicine that the patient is to receive as an injection, or as an infusion (a drip) into the veins. The doctor will decide the dose of the medicine that the patient should receive and for how long the patient will need to take. The dose will depend on the other medicine which is being dissolved or diluted with Sterilised Water for Injections. Sterilised Water for Injections can only be obtained on prescription. For further information on how Sterilised Water for Injections is used, please read section 3 of the package leaflet, available on the MHRA website. What benefits of Sterilised Water for Injections have been shown in studies? No clinical studies have been conducted as Sterilised Water for Injections contains no active ingredients and it is a well-known diluent. Its benefits and risks, when used as approved, are taken as being the same as those of the medicines it is used to dissolve or dilute. What are the possible side effects of Sterilised Water for Injections? Like all medicines, this medicine can cause side effects, although not everybody gets them. 2

3 If given on its own, intravenous injection of Sterilised Water for Injections may cause damage to red blood cells (haemolysis). Reporting of side effects The patient s doctor should be consulted if the patient gets any side effects. This includes any possible side effects not listed in this report. Side effects can also be reported directly via The reporting of side effects can help provide more information on the safety of medicines. Why is Sterilised Water for Injections approved? It was concluded that that the use of Sterilised Water for Injections was effective in the use as a diluent to dissolve and dilute other drugs that require mixing with water before they can be given as an injection or an infusion (a drip). The MHRA decided that, for Sterilised Water for Injections, the benefits are greater than the risks and the grant of the Marketing Authorisation was recommended. What measures are being taken to ensure the safe and effective use of Sterilised Water for Injections? A Risk Management Plan has been developed to ensure that Sterilised Water for Injections is used as safely as possible. Based on this plan, safety information has been included in the Summary of Product Characteristics and the package leaflet for Sterilised Water for Injections, including the appropriate precautions to be followed by healthcare professionals and patients. Known side effects are continuously monitored. Furthermore, new safety signals reported by patients/healthcare professionals will be monitored/reviewed continuously. Other information about Sterilised Water for Injections. A Marketing Authorisation was granted in the UK to Bio Products Laboratory Limited on 15 August The full PAR for Sterilised Water for Injections follows this summary. For more information about treatment with Sterilised Water for Injections, read the package leaflet, or contact your doctor or pharmacist. This summary was last updated in October

5 INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products Regulatory Agency (MHRA) granted Bio Products Laboratory Limited a Marketing Authorisation for the medicinal product Sterilised Water for Injections (PL 08801/0057) on 15 August The product is a prescription-only medicine (POM) indicated for use as a vehicle for dilution and reconstitution of suitable medicinal products for parenteral administration. The application was submitted under Article 8.3 of Directive 2001/83/EC, as amended. Sterilised Water for Injections is a solvent and diluting agent. The product contains no active ingredient. No non-clinical or clinical data were submitted, which is acceptable given that this application was based on the product being a medicinal product that (i) contains no active ingredient and (ii) is used as a solvent and diluting agent. No new or unexpected safety concerns arose during review of information provided by the Marketing Authorisation Holder and it was, therefore, judged that the benefits of using Sterilised Water for Injections outweigh the risks and a Marketing Authorisation was granted. 5

6 PHARMACEUTICAL ASSESSMENT S. ACTIVE SUBSTANCE As the only constituent in this product is sterilised water for injections, no active substance data were submitted or required. P. DRUG PRODUCT Other ingredients The only constituent of this product is water for injections. No materials of human or animal origin are used in the production of Sterilised Water for Injections. No genetically modified organisms are used in the production of Sterilised Water for Injections. Pharmaceutical Development Sterilised Water for Injections has been developed according to the corresponding European Pharmacopoeia monograph, as a vehicle for dilution and reconstitution of suitable products for parenteral administration. Manufacturing Process An appropriate account of the manufacturing process has been provided. The manufacturing process has been validated at and has shown satisfactory results. Control of Finished Product The finished product specification is satisfactory and in line with the current European Pharmacopoeia. Test methods have been described and adequately validated, as appropriate. Batch data have been provided, which comply with the release specification. Container Closure System The product is packaged in Type I clear glass 5 ml vials closed with halobutyl rubber stoppers and aluminium overseals with polypropylene flip off tamper evident caps. The vials are packaged with the Patient Information Leaflet in cardboard outer cartons, in pack sizes of 2.5 ml and 5 ml vials. Not all pack sizes may be marketed. Satisfactory specifications and Certificates of Analysis have been provided for all packaging components. All primary packaging complies with the current European regulations concerning materials for parenteral use. Stability of the product Finished product stability studies were performed in accordance with current guidelines on batches of finished product packed in the packaging proposed for marketing. The data from these studies support a shelf-life of 4 years, with the storage conditions Do not store above 30 C. Do not freeze. From a microbiological point of view the product should be used immediately. Suitable post approval stability commitments have been provided to continue stability studies on batches of finished product. 6

7 Bioequivalence No bioequivalence studies have been submitted for this application for a parenteral product and none were required. Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labelling The SmPC, PIL and labelling are satisfactory from a pharmaceutical perspective. A package leaflet has been submitted to the MHRA along with results of consultations with target patient groups ( user testing ), in accordance with Article 59 of Council Directive 2001/83/EC, as amended. The results indicate that the package leaflet is well-structured and organised, easy to understand and written in a comprehensive manner. The test shows that the patients/users are able to act upon the information that the leaflet contains. MAA (Marketing Authorisation Application) Form The MAA form is satisfactory from a pharmaceutical perspective. Expert Report (Quality Overall Summary) The quality overall summary is written by an appropriately qualified person and is a suitable summary of the pharmaceutical aspects of the dossier. Conclusion The grant of a Marketing Authorisation is recommended. 7

8 NON-CLINICAL ASSESSMENT No non-clinical data have been submitted and none are required for this type of application. The product consists entirely of sterilised water. When used as indicated, the product is well established as a non-toxic liquid and has no pharmacological effect in itself. Non-clinical data is included by association in the dossier of the product it is intended to reconstitute. An Environmental Risk Assessment was not required for this application, given that the product contains water only. The grant of Marketing Authorisation is recommended. 8

9 CLINICAL ASSESSMENT CLINICAL PHARMACOLOGY No clinical pharmacology data have been submitted and none are required for this type of application. The product consists entirely of sterilised water. When used as indicated, the product is well established as a non-toxic liquid and has no pharmacological effect in itself. All safety and clinical efficacy data is included by association in the dossier of the product it is intended to reconstitute. EFFICACY No efficacy data have been submitted and none are required for this type of application. SAFETY No safety data have been submitted with this application and none are required. No new or unexpected safety concerns arose from this application. PHARMACOVIGILANCE SYSTEM AND RISK MANAGEMENT PLAN The Applicant provided a Pharmacovigilance System Master File Summary (version 1.0, September 2012) stating that they have at their service a Qualified Person for Pharmacovigilance (QPPV) responsible for Pharmacovigilance who is suitably trained and aware of the responsibilities outlined in the current applicable European Union (EU) legislation. The QPPV has the necessary means for collection and notification of any adverse drug reaction occurring either in the Community or in a third country, and the means to fulfil all other requirements of current European Pharmacovigilance legislation. An acceptable Risk Management Plan has been provided. Routine risk minimisation is provided through the Summary of Product Characteristics and the Patient Information Leaflet and this is sufficient. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC), PATIENT INFORMATION LEAFLET (PIL) AND LABELLING The SmPC, PIL and labelling are acceptable from a clinical perspective. The PIL text is consistent with the details in the SmPC and in line with current guidance. The labelling is also in line with current guidance. CLINICAL EXPERT REPORT (CLINICAL OVERVIEW) A clinical overview has not been submitted and none is required for this type of application. CONCLUSION The grant of a Marketing Authorisation is recommended. 9

10 OVERALL CONCLUSION AND BENEFIT/RISK ASSESSMENT QUALITY The important quality characteristics of Sterilised Water for Injections are well-defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit/risk balance. NON-CLINICAL No non-clinical data were submitted and none is required for an application of this type. EFFICACY No non-clinical data were submitted and none is required for an application of this type. The product contains no active ingredient and is intended for the reconstitution of lyophilised medicinal products for parenteral administration. SAFETY No safety data was submitted and none is required for an application of this type. The product contains no active ingredient and is intended for the reconstitution of lyophilised medicinal products for parenteral administration. No new or unexpected safety concerns arose from this application. PRODUCT LITERATURE The SmPC, PIL and labelling are satisfactory and in line with current guidance. BENEFIT/RISK ASSESSMENT The quality of the product is acceptable, and no new non-clinical or clinical safety concerns have been identified. The benefit/risk balance is therefore considered to be positive. 10

11 Sterilised Water for Injections PL 08801/0057 STEPS TAKEN FOR ASSESSMENT 1 The MHRA received the Marketing Authorisation application on 10 January Following standard checks and communication with the applicant the MHRA considered the application valid on 06 February Following assessment of the application, the MHRA requested further information relating to the dossier on 27 February 2014 and 16 July The applicant responded to the MHRA s requests, providing further information on the dossier on 23 June 2014 and 01 August The application was granted on 15 August

12 SUMMARY OF PRODUCT CHARACTERISTICS In accordance with Directive 2010/84/EU, the Summaries of Product Characteristics (SmPCs) for products granted Marketing Authorisations at a national level are available on the MHRA website. 12

13 PATIENT INFORMATION LEAFLET In accordance with Directive 2010/84/EU, the Patient Information Leaflets (PILs) for products granted Marketing Authorisations at a national level are available on the MHRA website. 13

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